Association Between Germline Mutation in VSIG10L and Barrett's Esophagus/Esophageal Cancer

Key Points

  • The team used targeted next-generation gene sequencing to find a rare mutation (S631G) in the uncharacterized gene VSIG10L that segregated with disease in affected individuals with familial Barrett's esophagus.
  • Functional studies revealed that this mutation disrupts maturation of the normal esophageal lining.

Researchers at University Hospitals Case Medical Center have discovered that a rare genetic mutation is associated with susceptibility to familial Barrett's esophagus and esophageal cancer. The findings were published by Fecteau et al in JAMA Oncology.

Amitabh Chak, MD, of University Hospitals Case Medical Center's Seidman Cancer Center and Case Western Reserve University School of Medicine, and colleagues set out to identify novel disease susceptibility variants in familial Barrett's esophagus in affected individuals from a large multigenerational family.

The team used targeted next-generation gene sequencing to find a rare mutation (S631G) in the uncharacterized gene VSIG10L that segregated with disease in affected individuals with familial Barrett's esophagus. Functional studies revealed that this mutation disrupts maturation of the normal esophageal lining.

“Instances of esophageal cancer are on the rise, and the disease has a poor 5-year survival rate of less than 15%,” said Dr. Chak. “However, early detection through screening can prevent the development of esophageal cancer. Further research assessing this gene variant may reveal pathways important for the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma, leading to earlier detection and better treatment options.”

Discovery of this variant, which is the first susceptibility variant discovered in familial Barrett's esophagus, reveals novel biology in disease pathogenesis, and indicates early screening and close clinical monitoring for individuals harboring this germline variant.

“This is a step forward in combating this deadly disease as we discovered a new way to categorize those at risk for esophageal adenocarcinoma,” concluded Dr. Chak.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement